Nicotine and Caffeine Pouches for Fatigue

Age: 18 - 65

Sex: Male

Trial Phase: Academic

Sponsor: University of Southern Mississippi

Must not be taking: Insulin, Supplements, Nicotine, Caffeine

Disqualifiers: Diabetes, Heart disease, Hypertension, others

Compensation: Varies

Number of Visits: 4

Duration: 4 separate occasions

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how nicotine and caffeine pouches affect physical performance, cognitive skills, heart health, and appetite in healthy men. Researchers aim to determine differences between using nicotine pouches, caffeine pouches, both together, or a placebo. Participants will use these oral pouches and engage in cycling, cognitive, and balance tests while various health measurements are recorded. The trial seeks fit men aged 21-40 who exercise moderately or vigorously for at least 150 minutes a week. As an unphased trial, it offers participants the chance to contribute to understanding the effects of common substances on health and performance.

Will I have to stop taking my current medications?

The trial requires that you stop taking any supplements or medications that might interfere with the study results, and you cannot take medications that negatively interact with caffeine or nicotine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have found caffeine pouches to be generally safe for most healthy adults if total caffeine intake stays below 400 mg a day. However, they can cause side effects like jitteriness, anxiety, or a racing heart due to rapid caffeine absorption.

Nicotine pouches commonly cause side effects such as nausea, fatigue, or headaches. Although cases of nicotine poisoning have occurred, none were severe. Excessive nicotine can be harmful, so caution is necessary.

When combined, nicotine and caffeine might help with nicotine withdrawal and improve movement, according to research. However, both substances can cause side effects, which may intensify when used together. More research is needed to fully understand the effects of using both in pouches.

Overall, while these pouches are generally safe, they carry risks, and users should monitor their usage carefully. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional treatments for fatigue, such as lifestyle changes, sleep therapies, and medications like stimulants or antidepressants, these new oral pouches offer a unique approach. Researchers are excited about these treatments because they combine the familiar stimulants nicotine and caffeine in an innovative delivery method. The oral pouches provide a quick and convenient way to potentially boost energy levels without needing complex regimens or prescriptions. The combination pouch, delivering both nicotine and caffeine simultaneously, could amplify the energy-boosting effects more efficiently than current options.

What evidence suggests that this trial's treatments could be effective for fatigue?

This trial will evaluate the effects of different oral pouches on fatigue. Participants may receive oral caffeine pouches, which studies have shown can significantly improve physical performance by extending exercise duration and reducing tiredness. Caffeine also enhances thinking and decision-making, providing more mental energy. Another group will receive oral nicotine pouches, which research indicates do not significantly aid endurance but can improve skills requiring precise movements and boost short-term memory. Some participants will receive a combination of both nicotine and caffeine pouches, which may help maintain alertness and improve mood and movement, especially during withdrawal symptoms. Overall, both caffeine and nicotine offer unique benefits that could enhance performance and cognitive abilities. ^{2 6 7 8 9}

Who Is on the Research Team?

Austin J Graybeal, PhD

Principal Investigator

University of Southern Mississippi

Are You a Good Fit for This Trial?

This trial is for non-obese adult males aged 21-40 who want to participate in a study evaluating the effects of nicotine and caffeine pouches on physical performance, brain function, heart health, and appetite. Participants must be willing to use oral pouches and complete various tests.

Inclusion Criteria

Having a body mass index (BMI) of less than 30 kilograms/meter-squared

Participating in moderate/vigorous exercise for at least 150 minutes/week over the last month

I am between 21 and 40 years old.

Exclusion Criteria

I am missing a limb or part of a limb.

I take insulin injections.

Daily caffeine use of more than 250 milligrams/day or use of any oral caffeine pouches

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral nicotine and caffeine pouches or placebo and complete anaerobic cycling, cognitive, and balance tests

4 separate occasions

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 hours post each visit

What Are the Treatments Tested in This Trial?

Interventions

• Oral Pouch - Caffeine
• Oral Pouch - Nicotine
• Oral Pouch - Placebo

Trial Overview The study is testing how oral nicotine pouches, caffeine pouches, both combined, or placebo affect anaerobic performance (like cycling speed), cognition (thinking skills), cardiovascular/autonomic function (how the heart works), and food intake.

How Is the Trial Designed?

Group I: Oral Nicotine Pouches Experimental Treatment 1 Intervention

Single dose 3mg oral nicotine pouch

Group II: Oral Caffeine Pouches Experimental Treatment 1 Intervention

Single dose 100mg oral caffeine pouch

Group III: Combination of oral nicotine and caffeine pouches Experimental Treatment 2 Interventions

Single simultaneous doses of a 3mg oral nicotine pouch and a 100mg oral caffeine pouch

Group IV: Placebo Placebo Group 1 Intervention

Flavor, color, and appearance matched placebo

Who Is Running the Clinical Trial?

University of Southern Mississippi

Lead Sponsor

Trials

16

Recruited

3,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11435009/

The Effect of a Caffeine and Nicotine Combination on Nicotine ... The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ...

2. researchgate.net researchgate.net/publication/227750679_Effects_of_nicotine_and_caffeine_separately_and_in_combination_on_EEG_topography_mood_heart_rate_cortisol_and_vigilance

Effects of nicotine and caffeine, separately and in ... Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and ...

3. clinconnect.io clinconnect.io/trials/NCT06529055

Effects of Oral Nicotine and Caffeine Pouches on - ClinConnect This small, early-stage study is looking at how single-dose oral pouches containing nicotine, caffeine, or both affect exercise performance, thinking, mood, ...

4. wellnesspulse.com wellnesspulse.com/health-trends/are-caffeine-pouches-safe/

How Safe Are Caffeine Pouches? More studies are needed to determine the precise impact of nicotine or caffeine pouches on oral health, but dentists generally urge caution.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12377922/

The Effects of Oral Nicotine Pouches on Cigarette Smoking ... Compared to lower nicotine strength pouches, higher nicotine strength pouches may have greater impact on smoking behavior and adults who smoke ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10404176/

Oral nicotine pouches with an aftertaste? Part 1 Three substances were classified by International Agency for Research on Cancer as possibly carcinogenic to humans. The two nicotine-free ...

7. mdpi.com mdpi.com/2072-6643/16/18/3048

The Effect of a Caffeine and Nicotine Combination on ... The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability ...

8. theconversation.com theconversation.com/caffeine-pouches-deliver-a-fast-hit-and-hidden-risks-263933

Caffeine pouches deliver a fast hit – and hidden risks And because the drug is absorbed so quickly, side-effects, such as jitteriness, anxiety, insomnia and heart palpitations, can hit harder.

9. accessdata.fda.gov accessdata.fda.gov/static/searchtobacco/ZYN/PMTA_TPL_PM593-PM612_Zyn_01_13_2025_Redacted.pdf

TPL Review of PMTAs - accessdata.fda.gov The evidence related to appeal and intentions to use the new products, combined with observational data on youth use of nicotine pouches, ...